title: An improved radiolabelled RNA aptamer molecule for HER2 imaging in cancers.
abstract: Human epidermal growth factor receptor 2 (HER2) expression has been shown to be increased in several types of human tumours. In this study, for the imaging of HER2-related tumours, a modified RNA aptamer with HER2-specific targeting was labelled with (99m)Tc, by using hydrazino nicotinamide (HYNIC) as the chelator in the presence of tricine or ethylenediamine-N,N'-diacetic acid (EDDA) as the co-ligand. Stability testing of the radiolabelled aptamers in the serum was performed through SDS-PAGE. The aptamer-radionuclide conjugate was evaluated for its cellular HER2-specific binding in ovarian cancer cells (SKOV-3), and its biodistribution properties were assessed in normal and SKOV-3 tumour-bearing mice. In the presence of either tricine or EDDA, the HYNIC-RNA aptamers were labelled with (99m)Tc at a high yield and radiochemical purity. Cellular experiments confirmed the specific binding of the RNA aptamer to the HER2 receptor. In the animal biodistribution study, uptake of the EDDA-co-liganded (99m)Tc-HYNIC-RNA aptamer by the liver and spleen was remarkably lower than that of the aptamer with tricine. Tumours also showed a higher accumulation of radioactivity with the EDDA-co-liganded aptamer complex. This study demonstrated EDDA to be better than tricine for use as a co-ligand with the RNA aptamer, which can be a potential tool for the molecular imaging of HER2-overexpressing cancers.
authors.affiliation: Department of Radiopharmacy, Pharmaceutical Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences , Sari , Iran and.
authors.forename: Kambiz
authors.initials: K
authors.lastname: Varmira
authors.forename: Seyed Jalal
authors.initials: SJ
authors.lastname: Hosseinimehr
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Noaparast
authors.forename: Seyed Mohammad
authors.initials: SM
authors.lastname: Abedi
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D006834:Hydrazines / Q000378:metabolism; D007202:Indicators and Reagents / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008819:Mice, Nude; D057054:Molecular Imaging / Q000379:methods; D009536:Niacinamide / Q000031:analogs & derivatives / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000175:diagnosis*; D012313:RNA / Q000378:metabolism*; D019275:Radiopharmaceuticals / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D013667:Technetium / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D052157:Aptamers, Nucleotide; D005998:Glycine; D006834:Hydrazines; D007202:Indicators and Reagents; D008024:Ligands; D009536:Niacinamide; D012313:RNA; D019275:Radiopharmaceuticals; D018719:Erb-b2 Receptor Tyrosine Kinases; D013667:Technetium; C117288:hydrazino nicotinamide; C508053:ERBB2 protein, human; C100184:tricine